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作者：Nick Mulcahy  
出處：WebMD醫學新聞

　　December 11, 2009（德州聖安東尼奧）－ 臨床醫師對乳癌患者在以其他荷爾蒙治療仍然轉移後使用fulvestrant（Faslodex，阿斯特捷利康藥廠）可能需要考慮500 mg的劑量，而非目前核准的250 mg。
　　
　　發表在第32屆聖安東尼奧乳癌座談會（SABCS）的新數據顯示，較高劑量，相較於250 mg的劑量，可以提供統計上顯著較長的免於疾病惡化時間（6.5個月相較於5.5個月；P=0.006）。
　　
　　這些研究結果來自CONFIRM（Comparison of Faslodex in Recurrent or Metastatic Breast Cancer）研究。
　　
　　SABCS會議主任與CONFIRM研究發表記者會引言人C. Kent Osborne醫師表示，Fulvestrant是個些許被遺忘、或是至少有點相形見拙的乳癌荷爾蒙治療。
　　
　　德州休士頓貝勒醫學院Dan L. Duncan癌症中心主任Osborne醫師表示，fulvestrant的問題包括這是每個月使用一次的肌肉注射劑型，相較於每天使用口服荷爾蒙治療，芳香酶抑制劑是第一個被使用的。
　　
　　Osborne醫師解釋，在較早期的研究中，250 mg的fulvestrant對過去接受荷爾蒙治療後仍然惡化的雌性激素受體陽性乳癌病患，與anastrozole一樣好。
　　
　　然而，Osborne醫師表示，該藥物限制於使用tamoxifen與芳香酶抑制劑後惡化的轉移疾病患者，且在病患接受化學治療前能夠達到些許控制。
　　
　　這項研究的主要作者、義大利Prato醫院腫瘤部門的Angelo Di Leo博士解釋，這項使用500 mg fulvestrant的新研究並未改變這個藥物於荷爾蒙受體陽性乳癌患者在治療流程中的地位。
　　
　　Di Leo博士表示，這個藥物將仍然需要在tamoxifen與芳香酶抑制劑後使用。
　　
　　Osborne醫師表示，Fulvestrant已經被使用超過15年，但是這個藥物最好的時光還沒有到。
　　
　　Osborne醫師表示，長時間來一直都是這樣，但我們並不相信這個藥物已經被最佳地使用，他附帶表示，沒有被最佳地使用部分原因是與劑量有關。
　　
　　Osborne醫師也表示，Fulvestrant在抑制雌性激素上是「獨特的」，因為他可以摧毀雌性激素受體。
　　
　　他解釋，他可以更密集地降低雌性激素受體的表現。
　　
　　【先以抗雌性激素藥物治療與再發或惡化】
　　CONFIRM是一項隨機分派、雙盲、平行多中心第三期臨床研究，比較Fulvestrant兩種劑量使用於罹患雌性激素受體陽性進展性疾病女性，接受內分泌治療後，疾病再發或是惡化的機率。
　　
　　整體來說，736位女性（年齡中位數為61.0歲）在2005年到2007年之間從17個國家的128個中心收納到這項研究中。
　　
　　如果之前所說的，使用500 mg劑量Fulvestrant的病患們，相較於那些使用250 mg者，惡化所需時間顯著較長，換算為惡化風險下降20%（危險比值[HR]為0.80；95%信賴區間[CI]為0.68-0.94）。
　　
　　Di Leo博士在會議上表示，我們預期500 mg療程將會變成Fulvestrant的確立劑量。
　　
　　Di Leo博士表示，分析中6個事前定義的次組分析治療效果都是一致的。
　　
　　500 mg與250 mg劑量組的客觀反應率都是相似的（9.1%相較於10.2%；勝算比為0.94；95% CI為0.57-1.55；P=0.795）。接受500 mg劑量的病患，相較於那些接受250 mg的病患，在臨床好處上有許多優點（45.6%相較於39.6%；勝算比為1.28；95% CI為0.95-1.71；P=0.1），但是這並未達到統計上顯著差異。
　　
　　Di Leo博士指出，除此之外，接受500 mg劑量，相較於接受250 mg劑量的病患，在整體存活率上也有較好的趨勢（HR為0.84；95% CI為0.69-1.03；P=0.091），但之間的差距並未達統計上顯著差異。
　　
　　Di Leo博士表示，不良反應發生率或是嚴重度並沒有差異。
　　
　　研究者們目前正在進行Trans-CONFIRM研究，以研究是否所有病患或是僅有部分病患必須使用高劑量。
　　
　　Osborne醫師報告擔任Onyx藥廠的顧問。Di Leo博士表示擔任阿斯特捷利康藥廠的顧問團以及接受贊助。


Breast Cancer Hormonal Therapy With "Issues" Is Better at Higher Dose

By Nick Mulcahy
Medscape Medical News

December 11, 2009 (San Antonio, Texas) — Clinicians using fulvestrant (Faslodex, AstraZeneca) in breast cancer patients who have progressed to metastatic disease on other hormonal therapies might want to consider a 500?mg dose instead of the currently approved 250?mg dose.

New data presented here at the 32nd Annual San Antonio Breast Cancer Symposium (SABCS) show that the higher dose provided a statistically significantly longer time to disease progression than the 250?mg dose (6.5 vs 5.5 months; P?= .006).

The results come from the CONFIRM (Comparison of Faslodex in Recurrent or Metastatic Breast Cancer) trial.

Fulvestrant is a somewhat forgotten, or at least overshadowed, hormonal therapy for breast cancer, said C. Kent Osborne, MD, director of the SABCS meeting and moderator of the press conference during which the CONFIRM trial data were presented.

The issues with fulvestrant include the fact that it is a once-a-month intramuscular injection

"The issues with fulvestrant include the fact that it is a once-a-month intramuscular injection, as opposed to a daily oral hormonal therapy, and that aromatase inhibitors came along first," said Dr. Osborne, who is director of the Dan L. Duncan Cancer Center at Baylor College of Medicine in Houston, Texas.

In an earlier study, 250?mg of "fulvestrant was as good as [anastrozole]" in estrogen-receptor-positive patients with advanced disease who had progressed on previous hormonal therapy, explained Dr. Osborne.

Fulvestrant was as good as [anastrozole].

However, Dr. Osborne said, the drug is limited to metastatic patients who have progressed on tamoxifen and aromatase inhibitors and "allows some control before the patient goes on to chemotherapy."

The new results with 500?mg of fulvestrant do not change its place in the algorithm of hormone-receptor-positive breast cancer treatments, explained Angelo Di?Leo, MD, PhD, director of the Department of Oncology at the Hospital of Prato in Italy, and lead author of the CONFIRM study.

"It will still be used after tamoxifen and aromatase inhibitors," said Dr. Di?Leo.

Fulvestrant has been in use for 15 years, said Dr. Osborne. But its best days could be ahead, he suggested.

"It's been around for a long time but we don't believe it's been used optimally," said Dr. Osborne, adding that the suboptimal use was partly related to dose.

Dr. Osborne also noted that fulvestrant is "unique" among antiestrogens, because it can "destroy" the estrogen receptor.

"It can downregulate the estrogen receptor more intensively," he explained.

Pretreated With Antiestrogens and Recurring or Progressing

CONFIRM was a randomized double-blind parallel-group multicenter phase?3 study that compared the 2 doses of fulvestrant in postmenopausal women with estrogen-receptor-positive advanced disease recurring or progressing after previous endocrine therapy.

In total, 736 women (median age, 61.0 years) were recruited between 2005 and 2007 from 128 centers in 17 countries.

As mentioned, time to progression was statistically significantly longer for the patients receiving the 500?mg dose than for those receiving the 250?mg dose, corresponding to a 20% reduction in risk for progression (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.68?- 0.94).

We anticipate that the 500?mg regimen will become the established dose for fulvestrant.

"We anticipate that the 500?mg regimen will become the established dose for fulvestrant," Dr. Di?Leo told the meeting.

The treatment effect was consistent in the 6 predefined subgroups that were analyzed, said Dr. Di?Leo.

The object response rate was similar for the 500 and 250?mg groups (9.1% vs 10.2%; odds ratio, 0.94; 95% CI, 0.57?- 1.55; P?= .795). There was a numerical advantage in the clinical benefit rate for patients receiving the 500?mg dose, compared with those receiving the 250?mg dose (45.6% vs 39.6%; odds ratio, 1.28; 95% CI, 0.95?- 1.71; P?= .1), but it was not statistically significant.

Also, there was a "trend" for improved overall survival for patients treated with the 500?mg dose, compared with those treated with the 250?mg dose (HR, 0.84; 95% CI, 0.69?- 1.03; P?= .091), but the difference was not statistically significant, said Dr. Di?Leo.

There was no difference in severity or the incidence of adverse events, noted Dr. Di?Leo.

The investigators are currently conducting the Trans-CONFIRM study in an effort to understand whether the higher dose is mandatory in all patients or only in some.

Dr. Osborne reports being on the advisory board of Onyx Pharmaceuticals. Dr. Di?Leo reports being on the advisory board and receiving funding from AstraZeneca.

32nd Annual San Antonio Breast Cancer Symposium (SABCS): Abstract?25. Presented December?10, 2009.